Almost any cardiac disorder that impairs the ability of the ventricle to eject blood suffers a progression toward an inexorable deterioration of cardiac structure and function, producing the complex clinical syndrome of heart failure (HF), which is a common medical condition that afflicts approximately 1.5 to 2.0% of the population (4.8 million people in the United States) and which has a risk of death of 5 to 10% annually in patients with mild symptoms and increases to as high as 30 to 40% annually in patients with advanced disease, as, set for the in U.S. Pat. No. 6,440,078.
In recent years, physicians have prescribed implantation of conventional, atrioventricular (AV) synchronous pacing systems, including DDD and DDDR pacing systems, marketed by Medtronic, Inc. and other companies, in certain patients for treatment of HF symptoms. Certain patient groups suffering HF symptoms with or without bradycardia tend to do much better hemodynamically with AV synchronous pacing due to the added contribution of atrial contraction to ventricular filling and subsequent contraction. However, fixed or physiologic sensor driven rate responsive pacing in such patients does not always lead to improvement in cardiac output and alleviation of the symptoms attendant to such disease processes because it is difficult to assess the degree of compromise of cardiac output caused by HF and to determine the pacing parameters that are optimal for maximizing cardiac output, particularly the AV delay. Determining an optimal AV delay requires performing echocardiography studies or obtaining pressure data involving an extensive patient work-up as set forth in commonly assigned U.S. Pat. No. 5,626,623.
Data from external Holter monitors can determine if there is any accompanying electrical instability or arrhythmia. However, such Holter monitors cannot measure blood pressure or other indicia of mechanical heart function. Consequently, implantable physiologic cardiac monitors for monitoring the mechanical and/or electrical heart function have been proposed and, in some cases, implemented for deriving and storing EGM and mechanical performance data over a prolonged time.
In particular, the Medtronic® CHRONICLE® Implantable Hemodynamic Monitor (IHM) system comprises a CHRONICLE® Model 9520 IHM of the type described in commonly assigned U.S. Pat. No. 5,368,040 coupled with a Model 4328A pressure sensor lead that senses blood pressure within a heart chamber and the EGM of the heart using a pressure sensing transducer of the type disclosed in commonly assigned U.S. Pat. No. 5,564,434. The CHRONICLE® Model 9520 IHM measures absolute blood pressure, and the patient is also provided with an externally worn Medtronic® Model No. 2955HF atmospheric pressure reference monitor of the type described in commonly assigned U.S. Pat. No. 5,819,735 to record contemporaneous atmospheric pressure values.
The CHRONICLE® Model 9520 IHM can be programmed to measure the RV systolic pressure (maximum pressure in a sampling window), RV diastolic pressure (first sample in a sample window), pulse pressure (RV systolic—RV diastolic pressure), pre-ejection interval (PEI), systolic time interval (STI), peak positive and negative dP/dt, estimated pulmonary artery diastolic pressure (ePAD), patient activity level, and heart rate. The pressure parameters are sampled at a sampling rate of 256 samples per second, digitized and stored in memory registers. The samples are taken in a sampling window of each heart cycle of 20 ms through 500 ms following the detection of an R-wave, unless the R-wave occurs earlier. The Model 9520 IHM is programmed and interrogated employing an external Model 9790 programmer or a PC with CHRONICLE® software to accumulate trend data stored in a large FIFO buffer in RAM at a programmable resolution. The buffer can be filled in approximately an hour using the highest resolution or in about two months using the lowest resolution.
The memory buffers of the CHRONICLE® Model 9520 IHM and the externally worn Medtronic® Model No. 2955HF atmospheric pressure reference monitor can be interrogated to telemetry transmit the measured and stored pressure and other data, thereby emptying the buffers, to a nearby Model 9521HF Interactive Remote Monitor for temporary storage of the data. The Model 9521HF Interactive Remote Monitor external medical device periodically transmits accumulated data to a remote data processing center that processes the data to develop trend data that the attending physician can review with other patient data derived in patient examinations and interviews to assess the HF state.
In addition, the IHM system can be used in the clinical setting to make and observe real-time blood pressure and heart rate measurements while the patient is at rest or is exercising on a treadmill. The patient data can be stored in external clinical systems for historic or benchmark comparative uses over time.
Thus, such an IHM system implanted in patients suffering from cardiac arrhythmias or HF can accumulate date and time stamped blood pressure data that can be of use in determining the condition of the heart over an extended period of time and while the patient is clinically tested or is engaged in daily activities. Various other IHM functions and uses of EGM, pressure and other parameter data accumulated in an IHM are disclosed in U.S. Pat. Nos. 5,417,717, 6,104,949, 6,155,267, 6,280,409, 6,275,707, 6,309,350, and 6,438,408, for example. U.S. Pat. No. 5,758,652 describes an implantable absolute blood pressure monitor and method for measuring the heart condition of a patient by utilizing blood pressure signals filtered to remove respiratory effects.
It is estimated that perhaps as many as 20 million individuals in the United States have an asymptomatic impairment of cardiac function and are likely to develop symptoms of chronic HF in the next 1 to 5 years. The early identification and appropriate treatment of such individuals is highly desirable to achieve the greatest impact on individual and public health. One indicia of an early stage of chronic HF comprises ventricular afterload, which has not, to my knowledge been measured employing an IMD.
Ventricular afterload may be defined as the mechanical force opposing ventricular ejection, as for example described by W. R. Milnor, “Arterial Impedance as Ventricular Load” Circulation Research, 1975;36:565-70. This mechanical opposition of the flow of the viscous blood through the visco-elastic arterial system has two major mechanical components determined by the mechanical properties of the arterial system including hydraulic resistance and arterial compliance.
Hydraulic resistance is a function of several factors including the smooth muscle tone of the arterial system that determines arterial dimension, the dimensions and patency of the aortic or pulmonic valve, the geometry of the ventricular outflow tract, thickness of the ventricular myocardium, the length of the arterial vessels and the viscosity of the blood. Hydraulic resistance is proportional to ventricular afterload and can be described in general by Poisuelle's law or by Ohm's law, which states that systemic vascular resistance (also referred to as total peripheral resistance) is equal to the difference between mean arterial pressure and central venous pressure divided by cardiac output. Hydraulic resistance is typically estimated clinically by invasive or non-invasive estimates of mean arterial pressure and cardiac output.
Arterial compliance describes the ability of the arterial blood vessels to store a portion of the energy delivered to the arterial system by the ventricles during systole and return that energy to the arterial blood during ventricular diastole in order to maintain diastolic arterial blood pressure and flow. Arterial compliance is inversely proportional to ventricular afterload. Clinical estimates of arterial compliance are difficult to measure. It is occasionally approximated by aortic distensibility, or the change in aortic pressure divided by the change in aortic cross-sectional area. Another estimate of arterial compliance is “effective arterial elastance” as described for example by R .P Kelly et al., in “Effective Arterial Elastance as an Index of Arterial Vascular Load in Humans” Circulation 1992;86:513-521. Estimation of this parameter requires measurement of ventricular pressure and volume.
Ventricular afterload, including both arterial resistance and arterial compliance, may also be estimated using lumped or distributed mathematical models such as for example the three-element Windkessel model described by K .H. Wesseling et al., “Computation of Aortic Flow from Pressure in Humans Using a Non-linear, Three-element Model’, J. Appl. Physiol., 1993;74:425-35. The mathematical solution to these models requires measurement of both aortic blood pressure and flow.
The term “ventricular arterial coupling” describes the mechanical relationship between the ventricles and the arterial system during ventricular ejection as described for example by M .R. Starling, “Left Ventricular-arterial Coupling Relations in the Normal Human Heart”, Am. Heart J., 1993;125:1659-66. Cardiovascular function may be maintained even if ventricular contractile function is reduced by a compensatory decrease in ventricular afterload (either by decreased resistance, increased compliance or both). For example, administration of nitroglycerin during an episode of myocardial ischemia can maintain cardiac output despite decreased ventricular contractility by reducing arterial tone, increasing arterial compliance and hence decreasing ventricular afterload. Measurement of ventricular arterial coupling parameters involves measurement of both ventricular pressure and volume.
Regional or global changes in ventricular afterload including arterial resistance and compliance may alter patterns of arterial wave reflection. These changes in arterial wave reflection patterns may be manifest by changes in pressure signals measured in the arteries or ventricles as demonstrated for example by M. O'Rourke, “Coupling Between the Left Ventricle and Arterial System in Hypertension”, Eur. Heart J. 1990;11(G):24-28. Thus, changes in the morphometry of ventricular or arterial blood pressure signals can indicate changes in the resistive and compliant properties of the arterial system and hence can indicate changes in ventricular afterload.
The core of the altered cardiovascular function in HF is a depression of cardiac contractility. Therefore, an adequate assessment of cardiovascular function, including right or left ventricular afterload, has important diagnostic and therapeutic implications. Patients with acute HF, particularly as a complication of acute myocardial infarction or as an acute exacerbation of a previously compensated chronic HF, have a high mortality rate of about 30% within the first 12 months. In this clinical condition, a proper evaluation of ventricular afterload is extremely important for diagnostic purposes to assess the severity of the process and as a guide for the inotropic, vasodilator, or diuretic therapy. Typically, resistance indices are used to evaluate ventricular afterload, such as systolic arterial blood pressure, systemic vascular resistance or peak ventricular wall stress, with the serious limitations that these parameters have, since they ignore arterial compliance. Ventricular afterload may be estimated using aortic (or pulmonary) input impedance. However, this index requires the measurement of both pressure and flow and is difficult to interpret clinically.
Multiple clinical pathologies may result in acute or chronic changes in ventricular afterload including valvular disease, hypertension, ventricular hypertrophy, hypertrophic cardiomyopathy, atherosclerotic plaque formation, arterial thrombus, systemic shock, etc. In addition any vasoactive substance that affects arterial or venous tone, such as but not limited to nitro-glycerin, sodium nitro-prusside, neosynephrine, or epinephrine, can dramatically alter ventricular afterload. Hence, the ability to monitor and minimize ventricular afterload by minimizing arterial resistance, maximizing arterial compliance and controlling the timing of reflected waves by pharmacological or other methods is extremely important.